research papers Structures of artificial sweeteners – cyclamic acid ...

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Acta Crystallographica Section B 

Structural 

Science 

ISSN 0108-7681 

Ivan Leban, a * Darja Rudan- 

Tasič, b Nina Lah a and Cveto 

Klofutar b 

a Faculty of Chemistry and Chemical Technology, 

University of Ljubljana, SI-1000 Ljubljana, 

Slovenia, and b Biotechnical Faculty, 

University of Ljubljana, SI-1000 Ljubljana, 

Slovenia 

Correspondence e-mail: 

ivan.leban@fkkt.uni-lj.si 

# 2007 International Union of Crystallography 

Printed in Singapore – all rights reserved 

Structures of artificial sweeteners – cyclamic acid 

and sodium cyclamate with other cyclamates 

In the course of a study on artificial sweeteners, new crystal 

structures of cyclamic acid, sodium cyclamate, potassium 

cyclamate, ammonium cyclamate, rubidium cyclamate and 

tetra-n-propylammonium cyclamate have been determined. 

Cyclamic acid exists in its zwitterionic form in the crystalline 

state. The zwitterions are connected through hydrogen bonds 

of the N—H O type to form two-dimensional sheets. The 

sodium, potassium, ammonium and rubidium cyclamates are 

isostructural, with the cyclamate moieties linked through 

hydrogen bonds into linear chains. Taking into account the 

connectivity through cations, two-dimensional layers with a 

hydrophobic surface are constructed. In tetra(n-propyl)ammonium 

cyclamate the large, non-coordinating cation apparently 

prevents the formation of chains and thereby facilitates 

the centrosymmetric head-to-head discrete dimeric arrangement 

of the cyclamate moieties. 

1. Introduction 

Artificial sweeteners are chemical compounds classified as first 

generation (saccharin, cyclamate and aspartame) and new 

generation (acesulfame-K, sucralose, alitame, neotame and 

other sweet proteins). The sweet taste of cyclamates was 

discovered serendipitously by Sveda in 1937 (Audrieth & 

Sveda, 1944) and they were introduced commercially in the 

1950s. Today, cyclamic acid in the form of its sodium or 

calcium salt is one of the most widely used artificial sweeteners 

in food and pharmaceuticals. It is in use in more than 50 

countries, especially in combination with other sweeteners, to 

eliminate aftertaste (for example, the synergistic effect of 

saccharin–cyclamate; Verheyen, 1999; European Commission, 

2000, and references therein). However, the petition on 

cyclamic acid, calcium and sodium cyclamate is being held in 

abeyance with the FDA in the USA (CFSAN – Office of Food 

Additive Safety, 2006). 

Sweet-taste chemoreception originates in the interaction of 

a sweet molecule with a putative taste-bud receptor. 

Exhaustive studies have been performed in an attempt to 

rationalize the sweet taste of particular compounds and to 

correlate the structure/taste relationship. It is generally 

accepted that the molecule of sweetener must possess specific 

geometrical features. The classical theories (Shallenberger et 

al., 1969; Kier, 1972) presume the existence of a glucophore 

with three specific sites: a hydrogen-bond donor and acceptor 

(AH—B) and a hydrophobic part X. The sweet response is 

elicited through the interaction of such a glucophore with the 

complementary tripartite AH—B—X site in the taste-bud 

receptor. The tripartite glucophore concept (despite the 

neglect of the three-dimensional shape) has its merits as a 

Received 20 January 2007 

Accepted 22 March 2007 

418 doi:10.1107/S0108768107013961 Acta Cryst. (2007). B63, 418–425


Table 1 

Crystal and experimental for cyclamic acid (I), sodium cyclamate (II), potassium cyclamate (III), ammonium cyclamate (IV), rubidium cyclamate (V) 

and tetra-n-propylammonium cyclamate (VI). 

(I) (II) (III) 

Crystal data 

Chemical formula C 6H 13NO 3S Na + C 6H 12NSO 3 K + C 6H 12NSO 3 

M r 179.23 201.22 217.33 

Cell setting, space group Monoclinic, P2/c Monoclinic, C2/c Monoclinic, C2/c 

Temperature (K) 150 (1) 150 (1) 150 (1) 

a, b, c (A ˚ ) 8.1711 (10), 10.9972 (12), 9.4601 (11) 31.083 (6), 6.2718 (14), 8.5682 (17) 33.656 (8), 6.274 (3), 8.572 (4) 

( ) 91.575 (5) 94.481 (10) 93.350 (10) 

V (A ˚ 3 ) 849.72 (17) 1665.3 (6) 1807.0 (13) 

Z 4 8 8 

Dx (Mg m 3 ) 1.401 1.605 1.598 

Radiation type Mo K Mo K Mo K 

(mm 1 ) 0.34 0.40 0.79 

Crystal form, colour Plate, colourless Plate, colourless Prism, colourless 

Crystal size (mm) 0.24 0.24 0.07 0.20 0.18 0.08 0.13 0.13 0.12 

Data collection 

Diffractometer Nonius KappaCCD Nonius KappaCCD Nonius KappaCCD 

Data collection method ! scans at =55 ! scans at =55 ! scans at =55 

Absorption correction Multi-scan (based on symmetry- Multi-scan (based on symmetry- Multi-scan (based on symmetryrelated 

measurements) 

related measurements) 


Tmin 0.928 0.928 0.905 

Tmax 0.980 0.961 0.911 

No. of measured, independent and 

observed reflections 

10 483, 2195, 1955 10 594, 1923, 1480 75 861, 1953, 1565 

Criterion for observed reflections I >2 (I) I >2 (I) I >2 (I) 

Rint 0.033 0.049 0.043 

max ( ) 28.7 27.7 27.4 

Refinement 

Refinement on F 2 

F 2 

F 2 

R[F 2 >2 (F 2 )], wR(F 2 ), S 0.034, 0.090, 1.12 0.053, 0.130, 1.06 0.037, 0.090, 1.07 

No. of reflections 2195 1923 1953 

No. of parameters 108 113 113 

H-atom treatment Mixture of independent and 

Mixture of independent and 


constrained refinement 



Weighting scheme w = 1/[ 2 (F2 o) + (0.0224P) 2 + 0.7859P], 

where P =(F2 o +2F2 c )/3 

w = 1/[ 2 (F2 o) + (0.0356P) 2 + 6.6274P], 

where P =(F2 o +2F2 c )/3 

w =1/[ 2 (F2 o) + (0.0303P) 2 + 3.2501P], 

where P =(F2 o +2F2 ( / )max 

max, min (e A 

< 0.0001 < 0.0001 

c )/3 

0.001 

˚ 3 

) 0.47, 0.41 0.70, 0.56 0.36, 0.44 

(IV) (V) (VI) 

Crystal data 

Chemical formula NH þ 4 C 6H 12NSO 3 Rb + C 6H 12NSO 3 C 12H 28N + C 6H 12NSO 3 

M r 196.27 263.70 364.58 

Cell setting, space group Monoclinic, C2/c Monoclinic, C2/c Monoclinic, P2 1/n 

Temperature (K) 150 (1) 293 (1) 150 (1) 

a, b, c (A ˚ ) 33.6671 (19), 6.4571 (12), 8.7572 (15) 34.039 (5), 6.451 (2), 8.811 (2) 10.9510 (11), 13.5112 (12), 14.6202 (15) 

( ) 92.961 (2) 92.670 (10) 99.425 (5) 

V (A ˚ 3 ) 1901.1 (5) 1932.7 (8) 2134.0 (4) 

Z 8 8 4 

D x (Mg m 3 ) 1.371 1.813 1.135 

Radiation type Mo K Mo K Mo K 

(mm 1 ) 0.32 5.31 0.17 

Crystal form, colour Plate, colourless Plate, colourless Prism, colourless 

Crystal size (mm) 0.29 0.24 0.10 0.12 0.11 0.09 0.16 0.14 0.12 

Data collection 

Diffractometer Nonius KappaCCD Nonius KappaCCD Nonius KappaCCD 

Data collection method ! scans at =55 ! scans ! scans at =55 

Absorption correction Multi-scan (based on symmetry- Multi-scan (based on symmetry- Multi-scan (based on symmetryrelated 

measurements) 



Tmin 0.905 0.536 0.961 

Tmax 0.975 0.625 0.984 

No. of measured, independent 

and observed reflections 

24 925, 1936, 1650 10 240, 2549, 2327 25 465, 5074, 3955 

Criterion for observed 

reflections 

I >2 (I) I >2 (I) I >2 (I) 

Rint 0.045 0.039 0.044 

Acta Cryst. (2007). B63, 418–425 Ivan Leban et al. Structures of artificial sweeteners 419


Table 1 (continued) 

(IV) (V) (VI) 

max ( ) 26.4 29.1 27.9 

Refinement 

Refinement on F 2 

F 2 

F 2 

R[F 2 >2 (F 2 )], wR(F 2 ), S 0.042, 0.091, 1.20 0.024, 0.060, 1.10 0.041, 0.131, 1.06 

No. of reflections 1936 2549 5074 

No. of parameters 126 113 225 

H-atom treatment Mixture of independent and 






Weighting scheme w = 1/[ 2 (F2 o) + (0.0148P) 2 + 3.707P], 

where P =(F2 o +2F2 c )/3 

w = 1/[ 2 (F2 o) + (0.0179P) 2 + 2.7361P], 

where P =(F2 o +2F2 c )/3 

w = 1/[ 2 (F2 o) + (0.0713P) 2 + 0.5733P], 

where P =(F2 o +2F2 ( / )max 

max, min (e A 

Table 2 

Selected geometric data (A ˚ , ) for cyclamic acid (I), sodium cyclamate (II), potassium cyclamate (III), 

ammonium cyclamate (IV), rubidium cyclamate (V) and tetrapropylammonium cyclamate (VI). 

Compound (I) (II) (III) (IV) (V) (VI) 

S—O1 1.4290 (12) 1.457 (2) 1.4588 (16) 1.4610 (15) 1.4558 (14) 1.4560 (12) 

S—O2 1.4441 (11) 1.470 (2) 1.4592 (18) 1.4504 (16) 1.4526 (16) 1.4497 (12) 

S—O3 1.4407 (11) 1.448 (2) 1.4544 (18) 1.4472 (15) 1.4523 (15) 1.4645 (11) 

S—N 1.8003 (14) 1.643 (2) 1.641 (2) 1.6559 (18) 1.6401 (16) 1.6720 (14) 

N—C1 1.511 (2) 1.478 (4) 1.480 (3) 1.481 (3) 1.474 (2) 1.472 (2) 

C1—C2 1.521 (2) 1.532 (4) 1.530 (3) 1.526 (3) 1.515 (3) 1.522 (2) 

C2—C3 1.527 (3) 1.528 (4) 1.536 (3) 1.530 (3) 1.541 (3) 1.530 (2) 

C3—C4 1.523 (3) 1.533 (5) 1.525 (4) 1.522 (4) 1.515 (4) 1.523 (3) 

C5—C6 1.536 (3) 1.528 (4) 1.526 (4) 1.534 (3) 1.540 (4) 1.531 (3) 

C1—C6 1.524 (2) 1.531 (4) 1.527 (3) 1.525 (3) 1.520 (3) 1.522 (2) 

C2—C1—N—S 63.07 (15) 70.7 (3) 81.3 (2) 82.0 (2) 85.8 (2) 67.01 (16) 

O1—S—N—C1 155.71 (11) 168.4 (2) 174.77 (17) 179.30 (16) 174.57 (14) 151.49 (12) 

O2—S—N—C1 83.55 (11) 74.2 (2) 54.1 (2) 60.26 (18) 53.93 (17) 88.91 (13) 

O3—S—N—C1 34.70 (12) 46.9 (2) 67.0 (2) 61.09 (18) 67.25 (16) 31.70 (14) 

C1—C2—C3—C4 57.3 (2) 55.0 (4) 56.7 (3) 56.0 (3) 55.7 (3) 55.89 (19) 

C2—C3—C4—C5 56.6 (2) 54.6 (4) 55.5 (3) 55.3 (3) 54.6 (4) 53.9 (2) 

C3—C4—C5—C6 56.5 (2) 54.9 (4) 54.6 (3) 55.1 (3) 54.6 (4) 53.8 (2) 

C4—C5—C6—C1 57.4 (2) 56.4 (4) 54.8 (3) 55.5 (3) 54.7 (4) 56.3 (2) 

C5—C6—C1—C2 59.6 (2) 56.6 (3) 55.2 (3) 55.7 (3) 54.7 (3) 58.19 (19) 

C6—C1—C2—C3 59.41 (19) 55.4 (3) 56.1 (3) 56.2 (3) 55.7 (3) 57.76 (18) 

H—N—C1—H1a 176.6 175.1 169.8 164.4 162.8 71 (2) 

H—N—S—O1 82.0 (14) 64 (2) 43 (2) 52.0 (18) 44.2 (18) 28.5 (17) 

H—N—S—O2 38.7 (14) 53 (2) 78 (2) 68.5 (18) 76.4 (18) 148.1 (17) 

H—N—S—O3 157.0 (14) 174 (2) 161 (2) 170.2 (18) 162.4 (18) 91.3 (17) 

H1—NS—O1 32.9 (15) 

H1—N—S—O2 153.7 (15) 

H1—N—S—O3 88.1 (15) 

The labelling for the sulfamyl H atoms of cyclamic acid (I) has been changed slightly – H and H1 are attached to N. 

2. Experimental 

2.1. Sample preparation and crystallization 

Crystals of cyclamic acid were prepared by dissolving a 

sample of commercially available cyclamic acid (Sigma– 

Aldrich) in distilled water under gentle heating. Slow 

evaporation of water at ambient temperature produced 

transparent prismatic crystals of cyclamic acid (I) within 

2 weeks. Crystals of sodium cyclamate (II), potassium cyclamate 

(III), ammonium cyclamate (IV) and tetra-n-propylammonium 

cyclamate (VI) were obtained by slow evaporation 

of water from the aqueous solutions containing equimolar 

amounts of cyclamic acid and the corresponding hydroxide. 

Rubidium cyclamate (V) crystals were obtained by dissolving 

research papers 

cyclamic acid and Rb 2CO 3 in 

distilled water in a 2:1 molar ratio. 

On standing at ambient temperature 

colourless crystals appeared 

within a week. Crystals of several 

other cyclamates have also been 

prepared, but their limited quality 

did not allow a full X-ray structure 

determination (Leban et al., 2005). 

2.2. Data collection and structure 

determination 

All crystallographic measurements 

were performed on a Nonius 

Kappa CCD diffractometer 

(Mo K radiation, 55 kV, 30 mA) 

equipped with an Oxford Cryosystems 

Series 700 open-flow 

cryostat (Cosier & Glazer, 1986). 

The diffraction data [with the 

exception of that for the rubidium 

salt, 293 (1) K] were collected at 

150 (1) K. The standard strategy 

was used for data collection, cell 

refinement and data reduction 

(Hooft, 1998; Otwinowski & 

Minor, 1997). SIR92 (Altomare et 

al., 1993) and SHELXS97 (Sheldrick, 

1997) implemented in 

Version 1.64 of the WinGX program package (Farrugia, 1999) 

were used for structure solution by direct methods. 

SHELXL97 (Sheldrick, 1997) was used for structure refinement 

and the calculation of difference Fourier maps. The 

structures were refined by full-matrix least-squares against F 2 

using all data. H atoms have been located from the difference- 

Fourier maps and those of the sulfamate groups were refined 

isotropically without restraints. Those of the cyclohexane 

moieties and the tetra-n-propylammonium cation in (VI) were 

placed at calculated positions and treated as riding with Uiso 

values set to 1.2 or 1.5 Ueq of the parent atom. For visual 

interpretation and structural drawings the following programs 

were used: ORTEP3 for Windows (Farrugia, 1997), PLATON 

(Spek, 2003) and MERCURY (Macrae et al., 2006). Selected 

experimental and crystal data for cyclamic acid and reported 

cyclamates are given in Table 1. Inspection of the crystal data 

in Table 1 1 shows the isostructurality of sodium, potassium, 

ammonium and rubidium cyclamates. The separate structures 

of cyclamic acid (I), sodium cyclamate (II) and tetra-npropylammonium 

cyclamate (VI) together with molecular 

packing are depicted in Figs. 1, 2 and 3, respectively. In order 

to facilitate comparison, all atomic labelling was kept the 

same, the sulfamyl N atoms are marked as N, and the 

hydrogen attached to it is marked as H. The additional H atom 

1 Supplementary data for this paper are available from the IUCr electronic 

archives (Reference: BM5046). Services for accessing these data are described 

at the back of the journal. 



attached to N in cyclamic acid (I) is labelled as H1. The O3 

atom of each sulfo group is always positioned above the plane 

of the cyclohexane moiety, on the same side as H1A, H3A or 

H5A. Some selected geometric data generated by PARST 

(Nardelli, 1983, 1995) are collected in Table 2. 

3. Results and discussion 

3.1. Crystal structure of cyclamic acid (I) 

A prominent feature of cyclamic acid is that it can exist as a 

neutral molecule [see (Ia)] or in the zwitterionic form [see 

Figure 2 

ORTEP3 drawing (Farrugia, 1997) of sodium cyclamate (a) (displacement ellipsoids 

are drawn at the 50% probability level) and the crystal packing (b) and (c), where H 

atoms are omitted for clarity. 

(Ib)]. Analysis of the crystals of (I) has proved the existence of 

the zwitterionic structure (Fig. 1). The formulation was readily 

established by the straightforward identification of two Hatom 

sites adjacent to the N atom and it is further supported 

by a number of metrical features. The protonation of nitrogen 

affects the N—S bond length [1.8003 (14) A˚ ], which is significantly 

longer than the N—S distances observed in related 

compounds (Allen et al., 1995) and the cyclamates reported 

here. The S—O distances are 1.4290 (12), 1.4441 (11) and 

1.4407 (11) A˚ for S—O1, S—O2 and S—O3, respectively. The 

orientation of the sulfamyl group results in a torsion angle for 

S—N—C1—C2 of 63.07 (15) . Selected geometric 

parameters are listed in Table 2 and those of 

hydrogen bonding in Table 3. The two sulfamyl H 

atoms are involved in the formation of three 

hydrogen bonds of the N—H O type. The N— 

H2 O3 (symmetry code: x; y; z) hydrogen 

bond connects the molecules into centrosymmetric 

dimers, which are further linked into chains along 

the x axis through an N—H1—O2 (symmetry code: 

1 x; y; z) interaction. In addition, these 

chains are connected into two-dimensional layers 

through N—H2 O3 (symmetry code: 

1 x; y; z 2 ). Thus, the polar sulfamyl cores lie on a 

layer almost parallel to the ac plane, whereas the 

cyclohexane tails protrude from each side of the 

layer bringing the hydrophobic parts of adjacent 

layers together (Figs. 1 and 4). 

3.2. Crystal structures of Na + ,K + ,NH 4 + and Rb + 

cyclamates (II, III, IV, V) 

Sodium, potassium, ammonium and rubidium 

cyclamates are isostructural. A view of the asymmetric 

unit of sodium cyclamate (I) is depicted in 

Fig. 2. For clear comparison of the structures, the 

same atomic labelling scheme was used. A striking 

difference between the structure of the cyclamate 

anion and the cyclamic acid zwitterion is the S—N 

bond length. The S—N distances of 1.643 (2), 

1.641 (2), 1.6559 (18) and 1.6401 (16) A ˚ for (II), 

(III), (IV) and (V), respectively, are considerably 

shorter than that observed in cyclamic acid, 

1.8003 (14) A ˚ . A similar observation was made for 

the structures of sulfamic acid (Sass, 1960) and its 

ammonium salt (Cain & Kanda, 1972). Apparently, 

the free electron pair on the sulfamyl nitrogen in 

the cyclamate anion is involved in attractive interactions 

with the empty d orbital of the S atom, 

resulting in shortening of the S—N bond. The 

values of the S—N—C1—C2 torsion angles 

[70.7 (3), 81.3 (2), 82.0 (2), 85.8 (2) ] are higher 

than the corresponding torsion angle in cyclamic 

acid [63.07 (15) ], but the values differ significantly 

even within the group of four isostructural 

compounds. Thus, no conclusion regarding the 

orientation of the sulfamyl group can be drawn. 

422 Ivan Leban et al. Structures of artificial sweeteners Acta Cryst. (2007). B63, 418–425

Table 3 

Details of hydrogen bonding for cyclamic acid (I), sodium cyclamate (II) and tetra-npropylammonium 

cyclamate (VI). 


The single H atom on the sulfamyl N is 

involved in the formation of an inter- 

molecular N—H O3 (symmetry code: 

x; y; 1 

2 þ z) hydrogen bond that 

connects the cyclamate moieties into 

linear chains propagating along the b 

axis. 

The monovalent cations (Na + ,K + and 

Rb + ) are located between these chains 

and are coordinated predominantly by 

the O atoms of sulfo groups in such a 

way that two-dimensional layers are 

formed perpendicular to the a axis. The 

sodium cation in (II) is coordinated by 

six O atoms of five different sulfo 

groups. Five Na + O distances span a 

range between 2.302 (3) and 

2.480 (3) A˚ , whereas an additional 

oxygen is located at a longer distance 

[2.859 (3) A˚ ]. The potassium cation in (III) is ninecoordinated 

with eight K + O distances spanning 

the range 2.727 (2)–3.234 (2) A˚ and additionally 

the sulfamyl nitrogen is coordinated as a possible 

donor of a free electron pair to K + at 2.911 (2) A˚ . 

The rubidium cation in (V) was found to be tencoordinated 

by nine O atoms in the range 

2.916 (2)–3.332 (2) A˚ with the additional sulfamyl 

nitrogen at 3.052 (2) A˚ (Harding, 2002). The 

ammonium cation (NHþ 4 ) in (IV) serves as a Hatom 

donor for hydrogen bonds to the neighbouring 

sulfo O atoms, but the formation of 

hydrogen bonds does not influence the basic 

structural arrangement. There is no covalent 

interaction between the layers, which are separated 

from each other by the hydrophobic cyclohexane 

parts – protruding from both sides. It is 

interesting to note that the sodium, potassium, 

rubidium and ammonium cylamates are isostructural: 

because of the smaller size of the Na + cation, 

the sodium salt does not normally fit into such a 

series, as exemplified by alkali hydrogen acetylenedicarboxylates 

[Na + (Leban, 1974a); K + 

(Leban et al., 1973); Rb + (Blain et al., 1973); NHþ (I) (II) (VI) 

N O2 

4 

(Leban, 1974b)] and alkali naphthalenetetracarboxylates 

(Fitzgerald et al., 1993). 

i 

2.875 (2) N O3 iv 

3.061 (3) N O1 v 

2.983 (2) 

N—H1 0.91 (2) N—H 0.95 (4) N—H 0.73 (2) 

H1 O2 i 

1.98 (2) H O3 iv 

2.16 (4) H O1 v 

2.25 (2) 

N—H1 O2 i 

168 (2) N—H O3 iv 

159 (3) N—H O1 v 

173 (2) 

N O3 ii 

3.029 (2) 

N—H2 0.83 (2) 

H2 O3 ii 

2.26 (2) 

N—H2 O3 ii 

156 (2) 

N O3 iii 

3.030 (2) 

N—H2 0.83 (2) 

H2 O3 iii 

2.46 (2) 

N—H2 O3 iii 

127 (2) 

1 Symmetry codes: (i) x þ 1; y; z; (ii) x; y; þz 2 ; (iii) x; y; z; (iv) x; y; þz þ 1 2 ; (v) 1 x; 1 y; 1 z. 

Figure 3 

ORTEP3 drawing (Farrugia, 1997) of tetra-n-propylammonium cyclamate (a) 

(displacement ellipsoids are drawn at the 50% probability level) and the crystal 

packing (b) and (c). H atoms are omitted for clarity. Only anions are shown in (c). 

3.3. Crystal structure of tetra-n-propylammonium 

cyclamate (VI) 

The geometry of the cyclamate anion (Fig. 3) is 

similar to that observed for the other cyclamates 

reported here, however, the packing of the cyclamate 

moieties is influenced by the size and nature 

of the cation. Besides the greater size, the tetra-npropylammonium 

cation lacks the coordination 

abilities and the possibilities for the formation of 

hydrogen bonds. Thus, no extended arrangements 



are expected. The cyclamate units, related by the crystallographic 

inversion center, are connected to centrosymmetric 

dimers through N—H O interactions (Fig. 4), forming eightmembered 

R2 2ðÞrings 8 (Bernstein et al., 1995), which are 

already observed as a linking motif in (I). There are no other 

connections. The cyclamate moieties are arranged in columns 

of dimers, propagating along b, separated by columns of 

cationic moieties (Fig. 3). Comparison of the structures of 

cyclamate moieties in the reported cyclamates shows one 

significant difference. While the S—O3 and N—H groups in 

the sulfamate moieties are oriented trans to one another in 

sodium cyclamate (II) and in its isostructural compounds (III), 

(IV) and (V), the torsion angle N—H—S—O3 has a value of 

91.3 (17) in (VI). The orientation of the sulfamyl H atom is 

probably affected by the formation of centrosymmetric 

dimers, since the dimeric arrangement was also observed for 

cyclamic acid which contains two H atoms, one of which is in a 

Figure 4 

Graphic representation of the hydrogen bonding (MERCURY; Macrae et 

al., 2006) in (a) cyclamic acid (I), (b) sodium cyclamate (II) and (c) tetran-propylammonium 

cyclamate (VI). 

suitable orientation to form such dimers. Cyclamic acid as well 

as sodium and related cyclamates taste sweet, while the tetran-propylammonium 

salt tastes bitter. It seems that the position 

of the H atom on the sulfamyl nitrogen and consequently 

the hydrogen-bonding pattern is not the major ‘sweetness 

factor’, but the size and nature of the cation also possibly 

influences the sweetness. The remarkable structural feature 

common to all the sweet cyclamate species, but lacking in the 

bitter tetra-n-propylammonium salt, is the formation of twodimensional 

sheets with a hydrophobic surface. Additionally, 

in (VI) the hydrogen of the sulfamate moiety is attached on 

the other (of two) possible position at the N atom. 

4. Concluding comments 

The structural analyses of cyclamic acid and its five salts show 

similar geometry for the cyclamate moieties, but with different 

packing arrangements in the crystal. 

Generally, two types of packing were observed: 

(i) the formation of a layered two-dimensional structure 

with a hydrophobic surface and 

(ii) the discrete arrangement of cyclamate dimers without 

further interactions that would form extended arrangements. 

The latter was observed for tetra-n-propylammonium cyclamate, 

which alone among the reported compounds tastes 

bitter, while all others have a sweet taste. Nevertheless, 

additional data are needed to confirm the speculation that the 

packing in the solid state can also have an influence on the 

sweet-taste perception. 

These observations, together with previous investigations, 

show that the relationship between sweetness and structure is 

not an obvious one. This in turn means that the search for 

simple principles in the design of sweeteners will require 

further studies and considerably more sophisticated models 

than those currently available. However, we believe that the 

structural analyses of cyclamic acid and cyclamates will assist 

further research on the topic. 

The financial support of the Ministry of Higher Education, 

Science and Technology, Republic of Slovenia, through grants 

P1-0175-2005 and X-2000 is gratefuly acknowledged. 

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